Protective Role of Glutathione against Peroxynitrite-Mediated DNA Damage During Acute Inflammation.,Chemical Research in Toxicology

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Protective Role of Glutathione against Peroxynitrite-Mediated DNA Damage During Acute Inflammation.
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-09-07 , DOI: 10.1021/acs.chemrestox.0c00299
Nabeel Ahmed , Anindita Chakrabarty , F Peter Guengerich ₁ , Goutam Chowdhury

Affiliation

Inflammation is an immune response to protect against various types of infections. When unchecked, acute inflammation can be life-threatening, as seen with the current coronavirus pandemic. Strong oxidants, such as peroxynitrite produced by immune cells, are major mediators of the inflammation-associated pathogenesis. Cellular thiols play important roles in mitigating inflammation-associated macromolecular damage including DNA. Herein, we have demonstrated a role of glutathione (GSH) and other thiols in neutralizing the effect of peroxynitrite-mediated DNA damage through stable GSH-DNA adduct formation. Our observation supports the use of thiol supplements as a potential therapeutic strategy against severe COVID-19 cases and a Phase II (NCT04374461) open-label clinical trial launched in early May 2020 by the Memorial Sloan Kettering Cancer Center.

中文翻译：

谷胱甘肽对急性炎症期间过氧亚硝酸盐介导的 DNA 损伤的保护作用。

炎症是一种免疫反应，可防止各种类型的感染。如当前的冠状病毒大流行所示，如果不加以控制，急性炎症可能会危及生命。强氧化剂，如免疫细胞产生的过氧亚硝酸盐，是炎症相关发病机制的主要介质。细胞硫醇在减轻炎症相关的大分子损伤（包括 DNA）中起重要作用。在此，我们证明了谷胱甘肽 (GSH) 和其他硫醇在通过稳定的 GSH-DNA 加合物形成中和过氧亚硝酸盐介导的 DNA 损伤的作用中的作用。我们的观察结果支持使用硫醇补充剂作为针对严重 COVID-19 病例的潜在治疗策略，以及纪念斯隆凯特琳癌症中心于 2020 年 5 月上旬启动的 II 期 (NCT04374461) 开放标签临床试验。

更新日期：2020-10-21

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